For over forty years a number of medical devices which contact the blood or blood product of living persons or animals have been developed, manufactured and used clinically. A partial list of such articles would include pacemakers, arterial grafts, heart valves, artificial hearts, heart pumps, hip protheses, heart lung machines, catheters and kidney dialysis equipment.
A major problem with such articles is that their working surfaces, (i.e., surfaces which contact blood or blood products), are foreign to blood and blood products and tend to initiate, among other things, red cell destruction and coagulation of blood to form clots (thrombogenesis).
Normal intact endothelium is nonthrombogenic due partly to the synthesis of heparan sulfate. Heparan sulfate tends to remain bound to the surface of endothelial cells accelerating the inactivation of thrombin, the enzyme responsible for the polymerization of fibrinogen to fibrin in clot formation, by ATIII. Heparan sulfate is a very powerful anticoagulant in the natural vasculature. Consequently, it has been of great interest to physicians and the medical industry to devise blood-contacting polymeric surfaces that possess characteristics of heparan sulfate, specifically by coating surfaces with heparin. For example, in U.S. Pat. No. 3,826,678 to Hoffman et al., biologically active molecules are chemically bonded to polymers and copolymers which previously have been radiation-grafted to inert polymeric substrates such as a polyurethane and polyethylene. The grafted polymer is preferably a hydrophilic hydrogel e.g., hydroxyethyl methacrylate (HEMA) and may include heparin bonded to the hydrogel.
The thromboresistant or anticoagulation activity of heparin is believed to be due to the high concentration of anionic groups i.e., sulfonate (SO.sub.3 --) and carboxylic groups (COO--). It is further believed that a material or a surface containing appropriate amounts of sulfonate and carboxylic groups will demonstrate heparin-like activity. i.e. be a heparinoid material. In fact, Chun et al "Anticoagulation Activity of the Modified Poly(vinyl alcohol)" Polymer JournaI 22(4):347-354. (1990) demonstrated an anticoagulant activity of a blend of 60 wt % sulfonate poly(vinyl alcohol) (PVA) and 40 wt% carboxymethylated PVA.